The Effect of the Incretin Hormones on the Endocrine Pancreatic Function During Hyperglycemia in End-stage Renal Disease

NCT02237521 | Completed

• 1 other identifier: H-2-2014-021
• Study Type: observational
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with end-stage renal disease (ESRD) have a high prevalence of impaired glucose metabolism. The pathophysiological cause is uncertain, but disturbances in the secretion, elimination and effect of glucagon, insulin and the two incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), probably play important roles. Our research group has previously found that dialysis patients without type 2 diabetes mellitus (T2DM) have a reduced incretin effect and an inability to suppress glucagon after a meal - two early pathophysiological characteristics of patients with T2DM and normal kidney function. The aim of the project is to provide a detailed description of the mechanisms underlying the (patho)physiological effects of the incretin hormones in patients with ESRD. We plan to investigate the above mentioned disturbances during fasting and hyperglycaemic conditions using incretin infusions during glucose clamping. Furthermore, stable isotopic tracers will be used to determine the effect of the incretin hormones on the endogenous glucose handling. We hypothesise that the effects of the incretin hormones in ESRD will be reduced in respect to healthy control subjects.

Conditions

End-stage Renal Disease

Keywords

Incretin hormones; End-stage renal disease; ESRD; GLP-1; GIP; Insulin; Glucagon

Outcome Measures

Primary Outcomes (1)

• The effect of GLP-1 and GIP on insulin response during hyperglycemia between groups

  Average plasma insulin concentrations during hyperglycemia

  Average during the last 2 hours of each examination day. Blood samples are collected at time 122, 124, 126, 130, 210, 225 and 240 minutes

Secondary Outcomes (5)

• The effect of GLP-1 and GIP on insulin, glucagon and endogenous glucose production during euglycemia

  Average during the first 2 hours of each examination day. Blood samples are collected at time 90, 105 and 120 minutes

• The effect of GLP-1 and GIP on early and late phase of insulin, glucagon and endogenous glucose production during hyperglycemia

  Averages during the last 2 hours of each examination day. Blood samples are collected at time 122, 124, 126, 130, 210, 225 and 240 minutes

• The effect of GLP-1 and GIP on insulin and glucagon response to arginine

  Average following ariginine bolus. Blood samples are collected at time 242, 244, 246 and 250 minutes

• The effect of GLP-1 and GIP on the peripheral glucose handling

  Average during the first 4 hours of each examination day. Blood samples are collected at 5-15 minutes interval from time 0 to time 240 minutes

• The effect of GLP-1 and GIP on potassium concentrations during euglycemia

  Average during the first 2 hours of each examination day. Blood samples are collected at time 30, 60, 90 and 120 minutes

Study Arms (2)

End-stage renal disease

Patients with normal glucose tolerance and end-stage renal disease

Other: Eu- and hyperglycemic clamp; Other: Arginine test

Controls

Healthy controls with normal kidney function and normal glucose tolerance

Other: Eu- and hyperglycemic clamp; Other: Arginine test

Interventions

Eu- and hyperglycemic clamp OTHER

Eu- and hyperglycemic clamp with concomitant infusion of the natural occurring hormones glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) or placebo along with stable glucose isotope infusion to measure the effects of the incretins.

Controls; End-stage renal disease

Arginine test OTHER

Bolus infusion of the natural occurring amino acid arginine to measure the ability to increase the secretion of insulin and glucagon

Controls; End-stage renal disease

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

1. End-stage renal disease patients receiving chronic hemodialysis treatments 2. Healthy control subjects

You may qualify if:

• Chronic hemodialysis-dependent uremia in more than 3 months
• Normal kidney function

You may not qualify if:

• Fasting plasma glucose ≥ 6.1 mmol/l
• h plasma glucose ≥ 7.8 after ingestion of 75 grams of glucose
• Admittance to a hospital
• Anemia (Hb \< 6.0 mmol/l)
• Ongoing treatment with drugs interfering with glucose metabolism including steroids and calcineurin inhibitors
• Bowel resection or any other large abdominal surgery

Sponsors & Collaborators

• Bo Feldt-Rasmussen: lead

Study Sites (1)

Department of Nephrology, Rigshospitalet

Copenhagen, 2100, Denmark

Location

Biospecimen

Retention: SAMPLES WITH DNA

Serum, plasma and urine

MeSH Terms

Conditions

Kidney Failure, Chronic; Insulin Resistance

Interventions

Arginine

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential

Study Officials

• Morten B Jørgensen, MD

  Department of Nephrology, Rigshospitalet

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD DMSc

Study Record Dates

• First Submitted: August 29, 2014
• First Posted: September 11, 2014
• Study Start: September 1, 2014
• Primary Completion: April 28, 2016
• Study Completion: April 28, 2016
• Last Updated: May 22, 2017

Record last verified: 2017-05

Locations

DK (1)